CN103172802A - Diamino triazine hydrogen bond enhanced hydrogel based on cyclodextrin crosslinking and preparation method and application thereof - Google Patents
Diamino triazine hydrogen bond enhanced hydrogel based on cyclodextrin crosslinking and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a diamino triazine hydrogen bond enhanced hydrogel based on cyclodextrin crosslinking and a preparation method and an application thereof. The diamino triazine hydrogen bond enhanced hydrogel based on cyclodextrin crosslinking is prepared from 2-vinyl-4,6-diamino-1,3,5-triazine and beta-cyclodextrin with double bond through free radical polymerization and copolymerization; the two monomers and an initiator are dissolved in a solvent; unsaturated bonds on the molecules thereof are initiated by the initiator; and the hydrogel is prepared through a free radical polymerization reaction. The hydrogel disclosed by the invention has high stretch resistance and compression resistance and good biocompatibility.
Description
Technical field
The present invention relates to the hydrogel field, more particularly, relate to and have medicine and the bifunctional high intensity hydrogel of gene release and preparation method thereof, be beta-cyclodextrin and 2-vinyl-4, the 6-diaminostilbene, 3,5-triazine multipolymer (PCD-co-PVDT) preparation of gels and to its research as pharmaceutical carrier and genophore performance.
Background technology
Hydrogel be a class take water as dispersion medium, can absorb a large amount of moisture and can keep its original structure and the not dissolved polymkeric substance with three-dimensional net structure in water.Simultaneously, also have good water permeate, biocompatibility is Gu can reduce untoward reaction as body implant.Thereby hydrogel is used as good bio-medical material and is used widely.But for traditional hydrogel, relatively poor mechanical property has limited it as the biomaterial especially application of mechanics device.In recent years, there is Many researchers to be devoted to improve the mechanical property of hydrogel, dual network gel (J.P.Gong for example, Y.Katsuyama, T.Kurokawa, Y.Osada, Double-Network Hydrogels with Extremely High Mechanical Strength.Adv.Mater.15 (2003) 1155-1158), slip ring gel, nano composite material gel, four arms-polyethylene glycol gel, macromolecular microspheres plural gel, dipole-dipole strengthen gel, ion/covalent cross-linking gel and hydrophobic lamelliform plural gel etc.The technology of these bibliographical informations is mainly to be devoted to strengthen the intensity of hydrogel, as stretching, compression, ductility and energy-to-break etc.Recently, bibliographical information a series of high-strength gel (L.Tang based on diamino triazine hydrogen bond, W.Liu, G.Liu, High-Strength Hydrogels with Integrated Functions of H ?bonding and Thermoresponsive Surface-Mediated Reverse Transfection and Cell Detachment Adv.Mater.22 (2010) 2652-2656).Can form hydrogen bond in diamino three zin residues, cause the hydrogel physical strength to increase; Can in conjunction with plasmid DNA, be used for the gene transfection of reverse transfection or matrix-mediation in its surperficial diamino triazine component simultaneously.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art, provide a kind of not only can medicine carrying but also can carry the hydrogel of gene, be specially synthetic beta-cyclodextrin and 2-vinyl-4 with two keys, the 6-diaminostilbene, 3, the multipolymer of 5-triazine (PCD-co-PVDT), this hydrogel has higher stretch-proof and resistance to compression, and good biocompatibility.Study the medicine-releasing performance of PCD-co-PVDT hydrogel take Ibuprofen BP/EP (IBU) as the hydrophobicity model drug, investigated simultaneously the ability of its absorption plasmid DNA transfectional cell.
Technical purpose of the present invention is achieved by following technical proposals:
A kind of polyethyleneglycol modified monomer crosslinked high intensity hydrogel (strengthening hydrogel based on beta-cyclodextrin cross-linked diamino triazine hydrogen bond) of beta-cyclodextrin, by 2-vinyl-4, the 6-diaminostilbene, 3,5-triazine (VDT) and forming by the radical polymerization copolymerization with the beta-cyclodextrin of two keys, these two kinds of monomers and initiator are dissolved in solvent, cause unsaturated link(age) on their molecules by initiator, prepare hydrogel by Raolical polymerizable.
Its preparation method comprises the following steps:
At first, synthesizing polyethylene glycol Modified β-cyclodextrin linking agent.Adopt N, N '-carbonyl dimidazoles activated polyethylene glycol methacrylic ester (Mn=526, be PEG526MA), then add beta-cyclodextrin reaction at least 24 hours, reacted mixture is obtained target product PEG526MA-β-CD by dialysis and freeze-drying, shown in the following chemical equation of its reaction mechanism:
N wherein, the mass ratio of N '-carbonyl dimidazoles (CDI) and polyethylene glycol methacrylate-styrene polymer is 1:1, and temperature of reaction is 20-25 ℃, and preferred 24-30 of reaction times hour, adopting dimethyl sulfoxide (DMSO) (DMSO) was reaction solvent.
Secondly, prepare the method for hydrogel of the present invention, carry out according to following step:
With synthetic PEG526MA-β-CD, 2-vinyl-4, the 6-diaminostilbene, 3,5-triazine (VDT) and initiator are dissolved in solvent, cause the unsaturated link(age) of PEG526MA-β-CD and VDT by initiator, but prepare not only carrying medicament by Raolical polymerizable but also can be used as the hydrogel of genophore under the condition of starvation.
In technical scheme of the present invention, strengthen the more function of gel in order to give based on diamino triazine hydrogen bond, in this research, we are connected to two keys on beta-cyclodextrin, and it is formed gel as linking agent and VDT.Beta-cyclodextrin is by (β-CD) 7 D-glucopyranose units form by a kind of cyclic oligosaccharide that α-Isosorbide-5-Nitrae glycosidic link is formed by connecting, and there is a hydrophobic cavity its inside.By host-guest interaction, the cavity of beta-cyclodextrin can form inclusion compound with a lot of organic molecules, comprises medicine, nitrogen benzide and diamantane etc.With a plurality of pairs of keys, can be used as linking agent on the polyethylene glycol acrylate Modified β-cyclodextrin.The skeleton structure that is connected for " oxygen-carbon-carbon-oxygen " singly-bound in the middle of the polyethylene glycol acrylate molecular chain (is the backbone structure-(CH of peg molecule
2CH
2O)
n), to adopt thermal source or light source to make initiator that free radical is provided, then cause polyethylene glycol acrylate Modified β-cyclodextrin and 2-vinyl-4 by free radical, copolyreaction occurs in the two keys in 6-diamino-triazine.In the hydrogel material of final preparation, have polyethylene glycol acrylate Modified β-cyclodextrin and poly-2-vinyl-4, the segment of two kinds of materials of 6-diamino-1,3,5-triazines.Wherein, 2-vinyl-4 form a large amount of hydrogen bonds between a large amount of amino on 6-diamino-1,3,5-triazines molecule, greatly improved toughness and the intensity of hydrogel, plasmid DNA can be fixed on the surface of gel simultaneously, give the function of this gel load gene; Polyethylene glycol acrylate modified beta-cyclodextrin structure can not only provide flexible hydrophilic segment, and its hydrophobic cavity can the coated by hydrophobic medicine, can be used as pharmaceutical carrier.Above-mentioned two portions synergy makes whole hydrogel material embody biocompatibility and certain mechanical strength, and have simultaneously difunctional: namely can be used as pharmaceutical carrier again can the load gene.
Utilize free radical initiation VDT and the PEG526MA-β-CD linking agent that initiator provides to react.Wherein initiator can be selected thermal initiator commonly used in the high molecular polymerization field, as Diisopropyl azodicarboxylate (ABIN), benzoyl peroxide (BPO), perhaps light trigger, as the 1-[4-(2-hydroxy ethoxy)-phenylene]-2-hydroxyl-2 ', 2 '-dimethyl ethyl ketone (Irgacure2959), methyl vinyl ketone, st-yrax.If the selection thermal initiator needs at first to utilize the oxygen in rare gas element (as nitrogen, argon gas or helium) eliminating reaction system, avoid inhibition; Then according to activity and the consumption of initiator, reaction system be heated on the kick off temperature of initiator used and keep considerable time, as more than 1h or longer (1-5h), to guarantee that initiator can produce abundant free radical, the initiation reaction system continues Raolical polymerizable occurs, and finally prepares hydrogel of the present invention.If selective light initiator, can select transparent airtight reaction vessel, cause radical polymerization under the condition of UV-irradiation, due to light-initiated efficient higher than thermal initiation, need to adjust irradiation time according to activity and the consumption of selected initiator, irradiation time can be shorter than the heat-up time of thermal initiation, as 20 minutes or longer (30min-1h).
In technical scheme of the present invention, should be according to the solvability of the initiator of VDT, PEG526MA-β-CD and use, selection can dissolve fully above-mentioned three kinds of materials or can with above-mentioned three kinds of solvents that material dissolves each other fully, form the homogeneous reaction system, such as dimethyl formamide, N,N-DIMETHYLACETAMIDE, tetrahydrofuran (THF), dimethyl sulfoxide (DMSO) etc.
In the preparation scheme, during synthesizing polyethylene glycol acrylate Modified β-cyclodextrin linking agent, the molar ratio of polyethylene glycol methacrylate-styrene polymer and beta-cyclodextrin is (4-6): 1, and productive rate is 50%-70%.During the preparation gel, the mass ratio of VDT and PEG526MA-β-CD is (0.5-2): 1, preferred (1-2): 1, the quality of initiator is the 2%-4% of monomer and linking agent total mass (i.e. two kinds of monomers).After reaction finishes, take out multipolymer from reaction vessel, after removing monomer, initiator and the solvent of not participating in reaction, be immersed in water until reach swelling equilibrium (as soaking 7 days, change a water every 12h, reach swelling equilibrium).
A kind of high-strength PC D-co-PVDT hydrogel provided by the invention is polyethylene glycol acrylate Modified β-cyclodextrin and 2-vinyl-4, and the 6-diamino-1,3,5-triazines is raw material, and copolymerization is made under the initiator existence causes.Make hydrogel combine simultaneously poly-beta-cyclodextrin and 2-vinyl-4, the 6-diaminostilbene, 3, the character of 5-triazine, has very high water-intake rate, very strong stretch-proof and resistance to compression, has good physiologically acceptable, not only improve the mechanical property of gel but also plasmid DNA can be fixed on the surface of gel, reach the purpose of gene transfection, simultaneously polyethyleneglycol modified beta-cyclodextrin linking agent can improve the wetting ability of gel on the one hand, and the cavity of beta-cyclodextrin is conducive to the hydrophobic medicine realization of load control drug release on the other hand.This hydrogel (schematic arrangement as shown in Figure 1) at room temperature prepares, and the preparation method is simple, consumes energy low, and product is easy to prolonged preservation and long-distance transport.
Description of drawings
Fig. 1 is the schematic arrangement of hydrogel.
Fig. 2 be beta-cyclodextrin and polyethylene glycol acrylate Modified β-cyclodextrin at deuterium for the nuclear magnetic spectrogram in DMSO, wherein (1) is PEG526MA-β-CD, (2) are β-CD.
Fig. 3 is the infrared spectrogram of the attenuated total reflectance attenuated total refraction of different proportioning hydrogels, and wherein 1 is cr-PVDT; 2 is PCV1-2; 3 is PCV1-1.5; 4 is PCV1-1; 5 is PCV2-1.
Fig. 4 is that different proportioning hydrogels discharge the graphic representation of Ibuprofen BP/EP, wherein 1(square when normal temperature) be cr-PVDT; The 2(circle) be PCV1-2; The positive triangle of 3() be PCV1-1.5; The 4(inverted triangle) be PCV1-1; The 5(rhombus) be PCV2-1.Fig. 5 is that wherein A is PCV2-1 with the fluorescence photo of the different proportioning hydrogel absorption PVDT/pDNA mixtures of YOYO-1 mark, and B is PCV1-1, and C is PCV1-2.
Embodiment
Further illustrate technical scheme of the present invention below in conjunction with specific embodiment.
Wherein polyethylene glycol acrylate (PEGDA) can directly be bought (the Mn=526 from U.S. Sigma company, PEG526MA), adopt 4gN, N '-carbonyl dimidazoles (available from Tianjin prestige reagent company limited of section) activation 4g polyethylene glycol methacrylate-styrene polymer, then add 2g beta-cyclodextrin (available from Tianjin prestige reagent company limited of section) reaction 24 hours, temperature of reaction is 20-25 ℃, adopt DMSO as reaction solvent, reacted mixture by dialysis and freeze-drying, is obtained target product PEG526MA-β-CD.Fig. 2 be beta-cyclodextrin and polyethylene glycol acrylate Modified β-cyclodextrin at deuterium for the nuclear magnetic spectrogram in DMSO, instrument is UNITY plus-500NMRspectrometer (Varian, USA), wherein δ 4.8ppm is the hydrogen atom (being H1) that directly is connected with position carbon on cyclodextrin, δ 3.5-3.6ppm is the hydrogen atom that directly is connected with third place carbon on the H3(cyclodextrin), the hydrogen atom that directly is connected with No. five position carbon on the H5(cyclodextrin), the hydrogen atom that directly is connected with No. six position carbon on the H6(cyclodextrin); δ 3.2-3.3ppm is the hydrogen atom that directly is connected with No. two position carbon on the H2(cyclodextrin), the hydrogen atom that directly is connected with No. four position carbon on the H4(cyclodextrin) and HPEG; δ 4.4 (on cyclodextrin with hydroxyl that No. six position carbon directly is connected on hydrogen atom, i.e. O
6H), δ 5.7 (on cyclodextrin with hydroxyl that No. two position carbon directly is connected on hydrogen atom, i.e. O2H) with δ 5.6ppm (hydrogen atom on the hydroxyl that directly is connected with third place carbon on cyclodextrin, i.e. O
3H) be respectively proton peak on hydroxyl, at the upper a(δ 1.46ppm that occurs of nuclear-magnetism spectral line (1)) and b(δ 6.0ppm) be respectively on a position with the b position on the displacement of hydrogen.Result shows, having received on beta-cyclodextrin of polyethylene glycol acrylate success, and the substitution value on the beta-cyclodextrin hydroxyl is 71.4%.
With synthetic linking agent PEG526MA-β-CD(14mg), 2-vinyl-4, the 6-diaminostilbene, 3,5-triazine (7mg) joins in the 1.5ml centrifuge tube, after dimethyl sulfoxide (DMSO) (DMSO) dissolved monomer and linking agent with 200 μ l, add light trigger Irgacure2959(0.8mg, 1-[4-(2-hydroxy ethoxy)-phenylene]-2-hydroxyl-2 ', 2 '-the dimethyl ethyl ketone).To contain monomer, the solvent of linking agent and initiator adds in circular die, and mould shines 30min in the ultra-violet curing case, with abundant initiation radical polymerization.Open subsequently mould and take out gel, repeatedly rinse for several times with deionized water, and soaked 7 days, change above-mentioned deionized water every 12h.Test the water-intake rate of prepared hydrogel.Prepare the gel flap by same steps as, carry out mechanical property, coating medicine Ibuprofen BP/EP and cell experiment.This gel sample called after PCV2-1.Change the mass ratio of linking agent PEG526MA-β-CD and monomer VDT, carry out respectively quantitative measurement.For the gel in the embodiment of the present invention, we represent with PCVx-y, and x-y represents the mass ratio of PEG526MA--β-CD/VDT.
The equilibrium water absorption of gel records as follows: will suck with pan paper by the water of abundant soaked hydrogel surface in pure water, and then be placed on and claim to get weight in wet base m on balance
wet, then gel is placed on and carries out drying in baking oven, until reaching balancing side, weight gets dry weight m
dry, according to formula m
eq=(m
wet-m
dry)/m
wetThe equilibrium water absorption of * 100% calculated for gel, wherein m
wetAnd m
dryRepresent respectively weight in wet base and the dry weight of gel.The mechanical property of gel is tested with WDW-05 electric mechanical instrument, and the sample that carries out stretching mechanical property testing is of a size of 20mm * 2mm, and thick is 30 μ m.During test, gauge length and draw speed are fixed as 10mm and 100mm/min to reduce error.
Fig. 3 is the infrared spectrogram of the attenuated total reflectance attenuated total refraction of different proportioning hydrogels, adopts Nicolet380FT-IRspectrometer (USA) to measure.As can be seen from the figure, the feature peak position of PVDT: 3340cm wherein
-1Be the N-H stretching vibration; 2870cm
-1Stretching vibration for C-H; 1627cm
-1Be the C=N stretching vibration; 1022cm
-1It is the stretching vibration peak of the C-OH on beta-cyclodextrin.Prove thus being synthesized of PEG526MA-β-CD and monomer VDT copolymer hydrogel success.
Table 1 has been listed equilibrium water absorption, tensile strength and the compressive strength of different proportioning hydrogels, and as can be seen from the table along with the raising of VDT ratio, the mechanical property of hydrogel has significantly and increases, but water-intake rate descends thereupon.
The physical function parameter of the different proportioning hydrogels of table 1
Adopt following method that medicine carrying and the release ability of hydrogel are tested: to select hydrophobic Ibuprofen BP/EP to investigate Drug loading capacity and the encapsulation rate of hydrogel as drug model.At first with the gel freeze-drying, the gel with the certain mass freeze-drying is immersed in the Ibuprofen BP/EP solution of 2mg/mL at ambient temperature, soaks three days until hydrogel reaches balance.Then hydrogel is taken out, wash away the Ibuprofen BP/EP of its remained on surface.Then with the gel vacuum-drying after medicine carrying, place it in after drying in the water of 500 μ L, take out solution to certain hour, then add the water of equal volume.By visible-ultraviolet spectrometer, in the burst size of wavelength 223nm place's detection Ibuprofen BP/EP.Wherein, the quality of the quality/xerogel of Drug loading capacity=gel medicine carrying; The quality of the quality of encapsulation rate=gel medicine carrying/input medicine * 100%.
Table 2 has shown Drug loading capacity and the encapsulation rate of different proportioning hydrogels, and as can be seen from the table: in hydrogel, the content of beta-cyclodextrin is higher, and its Drug loading capacity and encapsulation rate are better.This is to form mixture because interact by host-guest between Ibuprofen BP/EP molecule and beta-cyclodextrin.Fig. 4 is that different proportioning hydrogels discharge the graphic representation of Ibuprofen BP/EP when normal temperature, and at front 20 hours, the release rate of all gels was all than comparatively fast, and this moment, drug release was mainly to be controlled by the swelling of hydrogel.After hydrogel reached balance, the rate of release of Ibuprofen BP/EP reduced along with the increase of linking agent polyethylene glycol acrylate Modified β-cyclodextrin content, shows the release that in hydrogel, beta-cyclodextrin can slow down Ibuprofen BP/EP.
Drug loading capacity and the encapsulation rate of the different proportioning hydrogels of table 2
Cr-PVDT(is PVDT) be 2-vinyl-4, the independent polymkeric substance of 6-diamino-1,3,5-triazines monomer adopts the preparation technology parameter identical with multipolymer to be prepared
Adopt following method to utilize hydrogel to carry out cell experiment, the gel that obtains is immersed medical alcohol, put into 48 orifice plates after irradiation sterilization in 20 minutes under ultraviolet lamp, add 500 μ lDMEM substratum to displace medical alcohol.With the gel of the present invention preparation immerse DMEM substratum 24 as a child after, the PVDT/pDNA mixture of certain volume is joined in the orifice plate of gel.20 ℃ of absorption joined the COS-7 cell suspension that is cultured to exponential phase of growth in the gel that has adsorbed DNA after 24 hours, cultivated after 24 hours, changed nutrient solution and cultivated 24 hours, and lysing cell, measure uciferase activity wherein afterwards.
Fig. 5 is the fluorescence photo of the different proportioning hydrogel absorption PVDT/pDNA mixtures of YOYO-1 mark, adopts olympus, and the CKX41 fluorescent microscope is taken pictures.Result shows: counting of green fluorescence increases along with the increase of VDT content; Show that VDT content is higher, the PVDT/pDNA mixture fixing in gel surface is more.Table 3 has been listed different proportioning hydrogels absorption PVDT/pDNA compound-mediated in-vitro transfection COS-7 cell expressing luciferase reporter genes and gel to the toxicity (cytotoxicity instrument model SYNARGY HT) of COS-7 clone, therefrom can find out: in gel, VDT content is higher, and reverse transfection efficient is better; In the gel surface of preparation, the survival rate of cell can reach 80%, means that gel toxicity is lower.
Reaction times, temperature of reaction, initiation method and initiator amount when changing the preparation gel, the basic identical character of gel performance in the gel of final preparation and embodiment.
Above the present invention has been done exemplary description; should be noted that; in the situation that do not break away from core of the present invention, the replacement that is equal to that any simple distortion, modification or other those skilled in the art can not spend creative work all falls into protection scope of the present invention.
Claims (10)
1. strengthen hydrogel based on beta-cyclodextrin cross-linked diamino triazine hydrogen bond, it is characterized in that, by 2-vinyl-4, the 6-diaminostilbene, 3,5-triazine and forming by the radical polymerization copolymerization with the beta-cyclodextrin of two keys is dissolved in these two kinds of monomers and initiator in solvent, cause unsaturated link(age) on their molecules by initiator, prepare hydrogel by Raolical polymerizable under the condition of starvation.
2. according to claim 1 based on beta-cyclodextrin cross-linked diamino triazine hydrogen bond enhancing hydrogel, it is characterized in that, described beta-cyclodextrin with two keys is prepared according to following step: adopt N, N '-carbonyl dimidazoles activated polyethylene glycol methacrylic ester, then add beta-cyclodextrin reaction at least 24 hours, reacted mixture is made by dialysis and freeze-drying.
3. according to claim 2 based on beta-cyclodextrin cross-linked diamino triazine hydrogen bond enhancing hydrogel, it is characterized in that, in the process of preparation with the beta-cyclodextrin of two keys, described polyethylene glycol methacrylate-styrene polymer Mn=526, N, the mass ratio of N '-carbonyl dimidazoles and polyethylene glycol methacrylate-styrene polymer is 1:1, the molar ratio of polyethylene glycol methacrylate-styrene polymer and beta-cyclodextrin is (4-6): 1, temperature of reaction is 20-25 ℃, preferred 24-30 of reaction times hour, the employing dimethyl sulfoxide (DMSO) is reaction solvent, and productive rate is 50%-70%.
4. according to claim 1 based on beta-cyclodextrin cross-linked diamino triazine hydrogen bond enhancing hydrogel, it is characterized in that, described 2-vinyl-4, the 6-diaminostilbene, 3,5-triazine and be (0.5-2) with the mass ratio of the beta-cyclodextrin of two keys: 1, the quality of initiator is the 2%-4% of monomer and linking agent total mass.
5. according to claim 1ly strengthen hydrogel based on beta-cyclodextrin cross-linked diamino triazine hydrogen bond, it is characterized in that, described initiator is selected Diisopropyl azodicarboxylate or benzoyl peroxide, and the reaction times is 1-5h.
6. according to claim 1 based on beta-cyclodextrin cross-linked diamino triazine hydrogen bond enhancing hydrogel, it is characterized in that, described initiator is selected the 1-[4-(2-hydroxy ethoxy)-phenylene]-2-hydroxyl-2 ', 2 '-dimethyl ethyl ketone, methyl vinyl ketone or st-yrax, the reaction times is 30min-1h.
7. strengthen the preparation of gels method based on beta-cyclodextrin cross-linked diamino triazine hydrogen bond, it is characterized in that, carry out according to following step:
(1) adopt N, then N '-carbonyl dimidazoles activated polyethylene glycol methacrylic ester adds beta-cyclodextrin reaction at least 24 hours, and reacted mixture is made beta-cyclodextrin with two keys by dialysis and freeze-drying;
(2) with 2-vinyl-4, the 6-diamino-1,3,5-triazines, be dissolved in solvent with beta-cyclodextrin and the initiator of two keys, cause unsaturated link(age) on their molecules by initiator, prepare hydrogel by Raolical polymerizable under the condition of starvation.
8. according to claim 7 based on beta-cyclodextrin cross-linked diamino triazine hydrogen bond enhancing preparation of gels method, it is characterized in that, in described step (1), described polyethylene glycol methacrylate-styrene polymer Mn=526, N, the mass ratio of N '-carbonyl dimidazoles and polyethylene glycol methacrylate-styrene polymer is 1:1, the molar ratio of polyethylene glycol methacrylate-styrene polymer and beta-cyclodextrin is (4-6): 1, temperature of reaction is 20-25 ℃, preferred 24-30 of reaction times hour, the employing dimethyl sulfoxide (DMSO) is reaction solvent, and productive rate is 50%-70%; In described step (2), described 2-vinyl-4,6-diamino-1,3,5-triazines and be (0.5-2) with the mass ratio of the beta-cyclodextrin of two keys: 1, the quality of initiator is the 2%-4% of monomer and linking agent total mass.
9. according to claim 7 based on beta-cyclodextrin cross-linked diamino triazine hydrogen bond enhancing preparation of gels method, it is characterized in that, in described step (2), described initiator is selected Diisopropyl azodicarboxylate or benzoyl peroxide, reaction times is that 1-5h or described initiator are selected the 1-[4-(2-hydroxy ethoxy)-phenylene]-2-hydroxyl-2 ', 2 '-dimethyl ethyl ketone, methyl vinyl ketone or st-yrax, the reaction times is 30min-1h.
10. as claimed in claim 1ly strengthen the application of hydrogel in controlling the drug release field based on beta-cyclodextrin cross-linked diamino triazine hydrogen bond, it is characterized in that, described medicine is hydrophobic medicine, as Ibuprofen BP/EP.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104987473A (en) * | 2013-10-11 | 2015-10-21 | 天津大学 | Application of high-strength light sensitive hydrogel in action of adjusting cell attachment |
| CN105085960A (en) * | 2015-07-27 | 2015-11-25 | 天津大学 | Zinc-ion-responding high-strength hydrogel tube, and preparation method and application thereof |
| CN107857841A (en) * | 2016-09-22 | 2018-03-30 | 天津大学 | High intensity copolymer hydrogel based on acrylamido glycine amide and preparation method thereof |
| CN113683734A (en) * | 2021-09-03 | 2021-11-23 | 万华化学集团股份有限公司 | Preparation method of novel notch impact resistant photosensitive PC and application of novel notch impact resistant photosensitive PC in sun protection |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102675562A (en) * | 2012-05-16 | 2012-09-19 | 天津大学 | Polyethylene glycol macromonomer cross-linked high-strength hydrogel and photo-initiation radical polymerization process thereof |
-
2013
- 2013-04-10 CN CN201310123751.8A patent/CN103172802B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102675562A (en) * | 2012-05-16 | 2012-09-19 | 天津大学 | Polyethylene glycol macromonomer cross-linked high-strength hydrogel and photo-initiation radical polymerization process thereof |
Non-Patent Citations (2)
| Title |
|---|
| DAVID C. BIBBY ET AL: ""Mechanisms by which cyclodextrins modify drug release from polymeric drug delivery systems"", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
| LEI TANG ET AL: ""High-Strength Hydrogels with Integrated Functions of H-bonding and Thermoresponsive Surface-Mediated Reverse Transfection and Cell Detachment"", 《ADVANCED MATERIALS》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104987473A (en) * | 2013-10-11 | 2015-10-21 | 天津大学 | Application of high-strength light sensitive hydrogel in action of adjusting cell attachment |
| CN104987473B (en) * | 2013-10-11 | 2017-09-19 | 天津大学 | Application of the high-strength light sensitive aquagel in regulation cell attachment behavior |
| CN105085960A (en) * | 2015-07-27 | 2015-11-25 | 天津大学 | Zinc-ion-responding high-strength hydrogel tube, and preparation method and application thereof |
| CN107857841A (en) * | 2016-09-22 | 2018-03-30 | 天津大学 | High intensity copolymer hydrogel based on acrylamido glycine amide and preparation method thereof |
| CN107857841B (en) * | 2016-09-22 | 2020-06-12 | 天津大学 | High-strength copolymer hydrogel based on acrylamide glycinamide and preparation method thereof |
| CN113683734A (en) * | 2021-09-03 | 2021-11-23 | 万华化学集团股份有限公司 | Preparation method of novel notch impact resistant photosensitive PC and application of novel notch impact resistant photosensitive PC in sun protection |
| CN113683734B (en) * | 2021-09-03 | 2022-08-05 | 万华化学集团股份有限公司 | Preparation method of notch impact resistant photosensitive PC and application of notch impact resistant photosensitive PC in sun protection |
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